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J Am Chem Soc ; 144(20): 8932-8937, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35576619


We completed the synthesis of dimeric high-oxidation-state securinega alkaloid flueggeacosine B via two synthetic routes from allosecurinine. The first-generation synthesis (seven overall steps) involved a Liebeskind-Srogl cross-coupling reaction for the union of two functionalized fragments, the organostannane and the thioester. As a means to further streamline the synthetic route, we have developed a visible-light-mediated Cu-catalyzed cross-dehydrogenative coupling (CDC) reaction between an aldehyde and an electron-deficient olefin. This enabled the second-generation synthesis of flueggeacosine B from allosecurinine in four overall steps. The newly developed CDC reaction paves a direct way to a conjugated dicarbonyl moiety, a ubiquitous structural moiety present in various natural products.

Alcaloides , Cobre/química , Securinega , Alcenos , Catálise , Paládio
Angew Chem Int Ed Engl ; 60(36): 19609-19613, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196083


A combined strategy of building blocks recognition and molecular network construction, termed the building blocks-based molecular network (BBMN), was first presented to facilitate the efficient discovery of novel natural products. By mapping the BBMN of the total alkaloid fraction of Flueggea suffruticosa, three Securinega alkaloids (SEAs) with unusual chemical architectures, suffranidines A-C (1-3), were discovered and isolated. Compound 1 characterizes an unprecedented 8/5/6/5/6/6/6/6-fused octacyclic scaffold with a unique cage-shaped 3-azatricyclo[,11 ]dodecane core. Compounds 2 and 3 are highly modified SEA dimers that incorporate additional C6 motifs. A hypothetical biosynthetic pathway for 1-3 was proposed. In addition, 1 significantly induced neuronal differentiation and neurite extension by upregulating eukaryotic elongation factor 2 (eEF2)-mediated protein synthesis.

Alcaloides/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Euphorbiaceae/química , Securinega/química , Alcaloides/química , Produtos Biológicos/química , Conformação Molecular
Nutrients ; 12(11)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182831


Securiniga suffruticosa is known as a drug that has the effect of improving the blood circulation and relaxing muscles and tendons, thereby protects and strengthen kidney and spleen. Therefore, in this study, treatment of Securiniga suffruticosa showed protective effect of inhibiting the vascular inflammation in human umbilical vein endothelial cells (HUVECs) by inducing nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) coupling pathway. In this study, Securiniga suffruticosa suppressed TNF-α (Tumor necrosis factor-α) induced protein and mRNA levels of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and Interleukin-6 (IL-6). Pretreatment of HUVEC with Securiniga suffruticosa decreased the adhesion of HL-60 cells to Ox-LDL (Oxidized Low-Density-Lipoprotein)-induced HUVEC. Moreover, Securiniga suffruticosa inhibited TNF-α induced intracellular reactive oxygen species (ROS) production. Securiniga suffruticosa also inhibited phosphorylation of IκB-α in cytoplasm and translocation of NF-κB (Nuclear factor-kappa B) p65 to the nucleus. Securiniga suffruticosa increased NO production, as well increased the phosphorylation of eNOS and Akt (protein kinase B) which are related with NO production. In addition, Securiniga suffruticosa increased the protein expression of GTPCH (Guanosine triphosphate cyclohydrolase Ⅰ) and the production of BH4 in HUVEC which are related with eNOS coupling pathway. In conclusion, Securiniga suffruticosa has a protective effect against vascular inflammation and can be a potential therapeutic agent for early atherosclerosis.

Anti-Inflamatórios/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inflamação/prevenção & controle , Extratos Vegetais/farmacologia , Securinega/química , Etanol/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Lipoproteínas LDL , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
Org Lett ; 22(9): 3673-3678, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32319780


Three pairs of Securinega alkaloid epimers with a piperidin-2-yl moiety (1-6) were isolated from Flueggea suffruticosa, and their structures including absolute configurations were definitely characterized. An interconvertible C-2' epimerization process within each pair of epimers was observed. The following comprehensive experimental and theoretical investigations demonstrated an unusual stereochemical inversion mechanism of an N-substituted carbon stereogenic center, which was evidenced to be a protic solvent mediated process involving a tandem 1,4-elimination/1,4-addition as the key step.

Alcaloides , Euphorbiaceae , Securinega , Alcaloides/química , Euphorbiaceae/química , Estrutura Molecular
PLoS One ; 15(3): e0229589, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155163


Securinega suffruticosa (Pall.) Rehd is an excellent natural secondary shrub in the Shell Islands of Yellow River Delta. The roots of S. suffruticosa have high medicinal value and are used to treat diseases, such as neurasthenia and infant malnutrition. Any organism that is isolated from this species is of immense interest due to its potential novel bioactive compounds. In this research, the distribution and diversity of culturable endophytic fungi in S. suffruticosa were studied, and the endophytic fungi with antimicrobial activity were screened. A total of 420 endophytic fungi isolates were obtained from the S. suffruticosa grown in Shell Islands, from which 20 genera and 35 species were identified through morphological and internal transcribed spacer (ITS) sequence analyses. Chaetomium, Fusarium, Cladosporium, and Ceratobasidium were the dominant genera. The high species richness S (42), Margalef index D' (5.6289), Shannon-Wiener index H' (3.1000), Simpson diversity index Ds (0.9459), PIE index (0.8670), and evenness Pielou index J (0.8719) and a low dominant index λ (0.0541) indicated the high diversity of endophytic fungi in S. suffruticosa, the various species of endophytic fungi with obvious tissue specificity. The inhibition percentages of the 12 species of such endophytic fungi against Colletotrichum siamense were 3.6%-26.3%. C. globosum, Fusarium sp.3, and C. ramotenellum had a high antibacterial activity against Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) were between 0.5 mg/mL and 2 mg/mL. Alkaloid content detection indicated that endophytic fungi had a high alkaloid content, whereas the alkaloid contents of C. globosum and Fusarium sp.3 reached 0.231% and 0.170%, respectively. Members belonging to the endophytic fungal community in the S. suffruticosa of Shell Islands that may be used as antagonists and antibacterial agents for future biotechnology applications were identified for the first time.

Endófitos/genética , Endófitos/fisiologia , Fungos/genética , Fungos/fisiologia , Plantas Medicinais/microbiologia , Securinega/microbiologia , Alcaloides/análise , Anti-Infecciosos/análise , Biodiversidade , China , DNA Fúngico/genética , DNA Fúngico/isolamento & purificação , Endófitos/isolamento & purificação , Fungos/classificação , Testes de Sensibilidade Microbiana , Filogenia , Rios
J Nat Prod ; 82(5): 1345-1353, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31082231


Seven new Securinega alkaloids, securingines A-G (1-7), together with seven known analogues (8-14), were isolated from the twigs of Securinega suffruticosa. Their chemical structures were elucidated by a combined approach of spectroscopic analysis, chemical methods, ECD calculations, and DP4+ probability analysis. The full NMR assignments and the absolute configuration of compound 8 are also reported. In addition, all the isolated phytochemicals (1-14) were assessed for their cytotoxic, anti-inflammatory, and potential neuroprotective activities. Compound 4 showed cytotoxic activity (IC50 values of 1.5-6.8 µM) against four human cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15). Compounds 3, 10, 12, and 13 showed potent inhibitory effects on nitric oxide production (IC50 values of 12.6, 12.1, 1.1, and 7.7 µM, respectively) in lipopolysaccharide-stimulated murine microglia BV-2 cells. Compound 5 exhibited a nerve growth factor production effect (172.6 ± 1.2%) in C6 glioma cells at 20 µg/mL.

Alcaloides/química , Alcaloides/farmacologia , Caules de Planta/química , Securinega/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Fator de Crescimento Neural/biossíntese , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , Ressonância Magnética Nuclear Biomolecular